DESCRIPTION: (Adapted from applicant's description) The research focus of this Center will be the elucidation of the genetic basis of polycystic ovary syndrome (PCOS), a major cause of infertility and metabolic disease. The Center will support an interactive research program including investigators from the University of Pennsylvania, the Pennsylvania State University Milton S. Hershey Medical Center and the University of California, San Francisco. The major hypothesis is that PCOS is caused by abnormal alleles at one or several loci which cause intrinsic defects in ovarian androgen biosynthesis. A secondary hypothesis is that defects in the insulin signal transduction system lead to insulin resistance and subsequent metabolic complications, but enhanced ovarian androgen synthesis. These hypotheses will be addressed by a molecular genetic approach to the identification of PCOS-related genes based on a genome-wide linkage analysis; the exploration of biochemical and molecular differences in normal and PCO human thecal cells including an analysis of mechanisms of regulation of ovarian androgen production by insulin and a novel protein (leptin) secreted by fat; post-translational regulation of the activity of P450c17, a key enzyme controlling androgen synthesis; and a study of the life history and metabolic sequelae of PCOS in different ethnic groups.